1-isonicotinyl-2-veratrylidene hydrazine



ie ift l-ISONICOTINYL-Z-VERATRYLIDENE HYDRAZWE Herman Herbert Fox,Passaic, N..l., assignor to Hoffmann-La Roche Inc, Nutley, NJ., acorporation of New Jersey No Drawing. Original application Mar. 7, 1952,Ser. No. 275,256 Divided and this application Dec. 6, 1957, Ser. No.700,987

1 Claim. (Cl. 260-295) This application relates to novel compounds whichare antitubercular agents. The invention embraces the compounds in theform of their free bases as well as acid addition salts thereof.

The compounds are:

The preparation of the compounds is illustrated by the followingexamples. Where the compounds are obtained in the form of the freebases, the latter can be readily converted to the acid addition salts ontreatment with acids, e.g., hydrochloric acid, hydrobromic acid, nitricacid, sulfuric acid, phosphoric acid, ethane sulfonic acid, tartaricacid, and the like. Where the compounds are isolated in the form of acidaddition salts, the latter can be converted to the free bases bytreatment with an alkali, for example, sodium hydroxide or ammoniumhydroxide. It is to be understood that the claims are to be construed asalso embracing salts of the bases.

Example 1 A mixture of 27.4 grams of isonicotinylhydrazine (which isalso known as isonicotinic acid hydrazide), 30 grams of piperonal, and200 cc. of water was warmed to about 50 C. and shaken. A solidprecipitate was formed, and the mixture was permitted to stand untilprecipitation was complete. The precipitate was then filtered ed andsuspended in hot isopropanol. On cooling the suspension,1-isonicotinyl2-piperonylidenehydrazine was obtained in the form ofcolorless prisms or fine needles; M.P. 236237 C.

Example 2 A mixture of 13.7 grams of isonicotinylhydrazine and 15 gramsof anisaldehyde was heated on a steam-bath. Partial solution occurredfollowed by solidification of the reaction mixture to producel-isonicotinyl-Z-(p-methoxybenzylidene) hydrazine. Upon crystallizationfrom xylene,

Patented Jan. 31, 1961 the compound was obtained in the form of lustrouswhite flakes; M.P. 17l.5-173.5 C.

Example 3 A mixture of 17.5 grams of isonicotinylhydrazine, 26 grams ofphenyl n-heptylketone, and cc. of methanol was refluxed for about 2hours. The reaction mixture was then concentrated to about one-halfvolume and cooled. l-isonicotinyl-2-(1 phenyloctylidene)hydrazineprecipitated and was filtered off. Upon recrystallization fromisopropanol-ligroin, the compound was obtained in the form of lustrouswhite needles which melted at 125.5- 126.5 C.

Example 4 A mixture of 40 grams of isonicotinylhydrazine, 40 cc. ofacetophenone, and 200 cc. of methanol was refluxed for 2 hours. Oncooling the reaction mixture,l-isonicotinyl-2-(ot-methylbenzylidene)hydrazine precipitated. It wasrecovered by filtration and crystallized from methanol: M.P. 173-173.5C.

Example 5 A mixture of 28 grams of isonicotinylhydrazine, 37 grams of3,4-dimethoxy-acetophenone, and 100 cc. of isopropanol was heated on asteam-bath to solution. On cooling the reaction mixture,l-isonicotinyl-Z-(oz-methylveratrylidene)hydrazine precipitated. It wasrecovered by filtration and crystallized from isopropanol; M.P.1895-1905 C.

Example 6 A mixture of 27.4 grams of isonicotinylhydrazine, 26.4 gramsof cinnamaldehyde, and 500 cc. of isopropanol was heated on a steam-bathto solution. On cooling the reaction mixture,1-isonicotinyl-2-cinnamylidenehydrazine precipitated as small yellowcrystals; M.P. 201-202 C.

Example 7 References Cited in the file of this patent Meyer et al.:Monatshefte fur Chemie, vol. 33 (1912), pp. 393-414.

Selikofl et al.: Quart. Bull. of Sea View Hospital, vol. XIII, No. 1(Jan. 1952), pp. 17-26.

Shchukina et al.: Chem. Abst. v01. 46 (1952), pp. 10431-10432.

